The major histocompatibility gene complex of man, HLA, controls the expression of several cell surface proteins that exist in many different forms; one of these is known as DR antigens. These molecules are structurally homologous to murine Ia antigens that have been implicated in regulating immune responses. Based on this similarity, and on the ability of anti-DR antisera to inhibit certain immune functions, it has been suggested that DR antigens also play a role in regulating immune responses by mediating cellular interactions among the various components of the immune system. In addition, the presence of a particular type of DR antigen often correlates with the incidence of specific diseases, some of which have an autoimmune aspect. Other diseases, such as certain malignancies, although presently associated with HLA-A, B antigens, may, upon further examination, reveal stronger associations with DR antigens. The aim of this proposal is to compare the structural variation of DR antigens isolated from several B lymphoid cell lines expressing different DR allotypes. Such studies may aid in deciphering the mechanism by which DR antigens confer susceptibility to disease. Furthermore, our results may provide an understanding of the role these molecules have in regulating cell-cell interactions required in the development of immune responses. This knowledge may provide the ability to manipulate the immune response in such a manner as to mitigate deleterious autoimmune responses or amplify beneficial immune responses to tumors.